Abstract 16091: Cardioprotective Actions of the N-Terminal-Derived Annexin-A1 Peptide, Ac2-26, Against Myocardial Infarction in vivo

Myocardial infarction (MI) is the major cause of heart failure and death in the Western world. Annexin-A1 is an endogenous, glucocorticoid-regulated anti-inflammatory protein. We have previously shown that this protein plays an important protective role in preserving left ventricular (LV) viability and function in vitro, actions that are reproduced by treatment with its N-terminal-derived peptide, Ac2-26. Little is known however about its cardioprotective actions in vivo, particularly beyond its early anti-necrotic actions in the first few hours of reperfusion. We now test the hypothesis that exogenous Ac2-26 limits multiple aspects of MI injury, over both the short and longer-term in vivo. In the first study, adult C57BL/6 mice were subjected to ischemia-reperfusion (left arterial descending coronary artery ligation, with 1-7 days reperfusion), and Ac2-26 was administered at 1mg/kg i.v. every 24h commencing 5mins before reperfusion. In the second study, mice were subjected to permanent coronary artery occlusion, with Ac2-26 administered 1mg/kg/day i.p. via osmotic pump inserted at time of surgery. As shown in the Table, Ac2-26 reduced cardiac necrosis after 24h reperfusion (infarct size, plasma troponin I levels), systemic and cardiac inflammation after 48h reperfusion (neutrophil and macrophage infiltration) and cardiac fibrosis after 7 days reperfusion. These protective actions at the level of cardiac morphology were associated with preservation of LV function 4wks after permanent occlusion, as determined on fractional shortening and velocity of circumferential fiber shortening. Taken together, our data is the first evidence of Ac2-26 cardioprotection beyond the first few hours of reperfusion in vivo, and importantly, the first to report Ac2-26-induced preservation of LV function in the heart post MI in vivo.